SRI International’s continuous flow SynFini™ Suite produced multiple nucleoside antivirals in a single day
Synthetic chemistry has greatly enhanced our health and well-being over the past two centuries, generating thousands of new medicines, agricultural compounds and industrial chemicals. Over this time however, the laboratory methods used to synthesize compounds have changed very little: They are still highly manual, frustratingly slow, and difficult to reproduce and scale. Automating these processes would expand availability of key compounds – including commonly used medications – while freeing chemists to focus on the next generation of life-enhancing molecules.
SRI developed a proprietary synthetic chemistry platform, the SynFini™ Suite, to automate the route design and synthesis of small molecule drug-like compounds. Using known procedures and machine learning, this multi-step, continuous suite of tools has demonstrated ability to dramatically streamline the chemical drug discovery and production process. SRI scientists recently used the SynFini platform to synthesize the nucleoside antivirals ribavirin, taribavirin, and tiazofurin consecutively over a 13-hour period, producing hundreds of milligrams of each product with no minimal manual intervention.
The SynFini Suite consists of three integrated components – SynRoute ™, SynJet™ and AutoSyn™ – that automatically design synthetic routes for molecules of interest, conduct subsequent reaction screening and optimization, and then produce the selected molecules on scales from micrograms to kilograms.
To synthesize ribavirin, taribavirin and tiazolfurin, SRI scientists first used SynRoute to propose synthesis strategies for producing ribavirin and its analogues in a flow chemistry format. They then performed an optimization study of the first step of ribavirin on SynJet, which helped determine the operating parameters for the continuous flow synthesis.
Finally, researchers developed the complete multistep synthetic procedure on AutoSyn, using it as a template for the synthesis of taribavirin, and demonstrated the SynRoute strategy for the three-step synthesis of tiazofurin. All three drugs were successfully synthesized in a 13-hour period – less than about a tenth of the time that is required to produce the same quantities of these drugs through manual chemical processes.